Sudden Cardiovascular Death

by Ben Best

THE DANGER OF SUDDEN DEATH

It is common to hear people say that they would most prefer to
die in their sleep, or at least prefer to die suddenly. For cryonicists
concerned about the effects of brain ischemia (loss of blood circulation)
and autolysis (dissolution of the brain in putrefaction), such a
scenario is a disaster.

On July 10, 1991 Jerry Leaf, Leader of the Alcor Suspension Team,
died suddenly at the age of 50 from a cardiac arrest. Despite the fact that
his death was witnessed, despite his years of work at the forefront of
cryonics
and despite the nursing expertise and rapid application of CPR by
his wife, Jerry experienced 6 hours of ischemia above 20°C. Sudden death
(even under the best of circumstances) makes a cryonicist a "coroner's case",
subject to legal delays before cryonic procedures can begin. More recently,
John Erfurt, a 58-year-old Director of the Cryonics Institute, experienced
sudden death on September 9, 1992. Although the medical examiner signed the
death certificate almost immediately, his body was not discovered until
several hours after clinical death. That such compromises of cryonic
rescue capability is possible even among the most committed of cryonicists
is a matter of serious concern.

Considerable autolysis can be expected of a person who is
discovered dead in bed many hours after the cessation of heartbeat.
Moreover, the blood vessels of the brain are very sensitive to loss of
oxygen. In less than an hour after deanimation it can become virtually
impossible to restart brain circulation by artificial means for the
purpose of perfusing the brain with cryoprotectants. Even in the early
stages, when recirculation is possible, reperfusion injury occurs if
too many minutes of ischemia have occurred.

The avoidance of sudden death should be a high priority for
cryonicists. A good suspension will involve a rescue team on
standby with knowledge that deanimation is immanent. Ideally, this will
occur outside of a hospital, with a co-operative nurse on duty who can
sign a death certificate without delay. There should be no danger of
becoming a "coroner's case" under these circumstances. Death is our
enemy, a sudden and unexpected death is our most deadly enemy. Know
your enemy! A greater knowledge of sudden death means a greater likelihood
that it can be avoided or dealt-with.

THE CAUSES AND FREQUENCY OF SUDDEN DEATH

In Roy Walford's book MAXIMUM LIFESPAN (1), he named the three
contemporary leading causes of death to be:
(1) heart disease (38.3%), (2) cancer
(17.2%),
and (3) stroke (10.8%). Only 2.8% of deaths were said to be caused by
motor vehicle accidents, and even these are not all sudden fatalities.

The most long-standing, large-scale and careful epidemiological
study of cardiovascular disease is the Framingham Heart Study, begun in
the city of Framingham, Massachusetts in 1948. Nearly half of the
original participants have now died, and their deaths have been
diagnosed with care (2). The Framingham definition of "sudden death"
is a death that occurs within one hour of the onset of symptoms, and
this definition is the most commonly used among medical researchers.
Sudden cardiac deaths (SCDs) accounted for 11% of Framingham deaths, with
another 7% classified as "possible" SCDs. ("Possible"
cardiac deaths are those which have not been witnessed, or those for
which the deceased was discovered dead in bed. These statistics are
supported by analysis of 1983 death certificates for the entire
state of Massachusetts (despite the fact of diagnosis being less
scrupulous)(3). A study based on data compiled from both Framingham
and civil servants in Albany, New York (4) demonstrated that for
men in the 45-75 age range, 60% of SCDs occurred
in men with no prior evidence of coronary artery disease. In another
study, 32% of deaths among men in the 20-64 age range was attributed to
SCD, with 25% showing no prior recognized symptoms of heart disease (5).

A detailed pathological study was made of 130 random subjects
who died suddenly in the Glasgow, Scotland area (6). 92 of these (70%)
sudden deaths were due to ischemic heart disease, 13 (10%) were due to
overdose, 8 (6%) were due to unknown causes and 6 were (4.6%) were due to
non-ischemic cardiovascular disease. Only two cases (1.5%) were due to
cerebrovascular disease (stroke). All of the subjects deemed to have died from ischemic
heart disease in the Glasgow Study showed a loss of more than 75% of
cross sectional area in one or more coronary arteries (arteries
supplying the heart).

Although stroke ranks third as a cause of
death in industrialized countries, only 15% actually die in the
acute phase -- and even those deaths are frequently not rapid enough
to be classified "sudden". Stroke is, however, the major cause of
disability, with over 50% of stroke survivors being permanently
disabled (7).

Atherosclerosis of the coronary arteries is the most common
form of heart disease. Fatty cholesterol deposits (atheroma) line the
walls of the arteries and are hardened (sclerosis) by deposits of
calcium or lime salts. Arterial walls can be further narrowed by the
clotting of blood (thrombosis). Clots that break loose and plug the
artery downstream are called emboli. A region of the heart deprived of
blood because a thrombus or embolus has stopped circulation is called a
myocardial infarct (dead or dying heart muscle). Myocardial infarction
is more commonly known as heart attack, whereas sudden cardiac death
is more commonly known as cardiac arrest.
Angina pectoris is a coronary atherosclerotic
disease characterized by chest pain during exertion, particularly in
cold weather. Although it can be relieved by nitroglycerin tablets (which
dilate coronary arteries), it represents an increased risk of heart attack
and cardiac arrest.

The most common sequence of events in an SCD is the slow progression of
coronary artery atherosclerosis until the blood supplied to the
heart ventricles is inadequate, stimulating further speedup of ventricular
contraction and causing the contractions to become spasmodic and irregular
(ventricular fibrillation). For this reason, cardiac arrest is sometimes
referred to as "arrhythmic death". 75 to 90% of patients experiencing
SCD are discovered to be in ventricular fibrillation
by mobile cardiac resuscitation teams (8).

Sudden cardiac death involves arrhythmia (irregular beating) of
the heart ventricles due to irregularity of electrical stimulation in those
ventricles. SCD requires both that the ventricles be vulnerable to electrical
instability and that some condition exists that can trigger that instability.
In most cases, the condition that triggers SCD is coronary artery disease
(CAD), but myocardial infarction is the trigger in less than 20% of
cases (5,9). Analyzing the electrical patterns of the heart during exercise
stress testing is the most effective means to determine the risk of
electrical instability that can lead to SCD. In one study, patients
demonstrating such electrical instability showed the greatest improvement
(and the least side effects) when given the antiarrhythmic drug Ethmozin (5).

Psychological stress can also be a factor leading to SCD. In one
cruel experiment, dogs placed in a sling and subjected to electrical shocks
demonstrated significantly more arrhythmias than a control group. After
conditioning, simply placing the dogs in a sling without such shocks was
enough to induce arrhythmias (5).

TIME AND PLACE OF SUDDEN DEATH

According to one study (10) only 10% of all cases of cardiac arrest occur
in a hospital, even among men with known coronary heart disease. Heart attack
can be every bit as dangerous as cardiac arrest, because nearly half of
heart attack victims die outside of a hospital -- despite a warning of two
hours or more. Typically the victims try to convince themselves that the
pressure, squeezing and pain in their chest isn't really a heart attack.
Chest discomfort may spread to the shoulders, neck and arms. A feeling of
weakness may accompany sweating, nausea and shortness of breath. But these
feelings may come and go -- and since the typical heart attack victim has
not had previous experience with having a heart attack, denial can be
convenient and easy.

The most common time of death from all causes is 8 am, with a
secondary peak at 6 pm. The pattern is similar for all people over 65, but
for males under 65, the peak times are midnight, 2 pm and 8 am, in that
order. For females under 65, peak times are 11 pm, noon and 8 am, in that
order. Peak death times for ischemic heart disease and cancer are 8 am,
but stroke death peaks at 6 am (11). It is possible that knowledge of such
statistics could be helpful in both understanding the mechanisms of death
and in planning strategies to prevent or deal-with death.

The Framingham Study (2) reveals that the risk of sudden cardiac
death is at least 70% higher during the 7 to 9 am period than the average
risk during other times of the day. This risk is similar for both sexes and
for all ages. Nor does it seem to vary with day-of-week or month-of-year.
And the rate of sudden cardiac death is lower during normal hours of
sleep (11 pm to 6 am) than during waking hours.

A study was made of the blood pressure and heart rate of people
with hypertension and normal blood pressure during continuous, 24-hour
monitoring (12). For all subjects blood pressure was lowest at 3 am, and
for all subjects the increase in blood pressure and heart rate was highest
between 7 am and 9 am. Hypertensive patients reached a peak blood pressure
at 10 am, which declined gradually during the day. People with normal
blood pressure had a steady blood pressure from 9 am to 6 pm, after which
a gradual decline was seen.

UNCONTROLLABLE RISK FACTORS FOR SUDDEN CARDIAC DEATH (SCD)

Genetic factors seem to be significant determinants in predisposing
certain people to sudden cardiac death (SCD), yet these cannot yet be
altered. Similarly, the likelihood of SCD is greatly influenced by age
and sex.

In the Framingham Study, the frequency of SCD increases slightly
more than linearly for men over age 35, whereas for women there is an
exponential increase over age 65. The incidence of SCD doubles every
decade after age 45, but women in their 60s experience the same rate
of SCDs as men in their 40s (13,14). In the 45 to 65 age range, the incidence
of SCDs in men is four times as great as that in women. Only 2.5% of
heart attacks by American women occur before the age of 65 (15). Estrogen
is seen as protective against heart disease, although another theory holds
that menstrual bleeding reduces the amount of iron in the circulation (which
has led some to suggest that the protection against heart disease afforded
by aspirin is due to gastric bleeding)(16). Iron is thought to damage heart
muscle and oxidize LDL cholesterol, causing it to stick to artery walls (16).

Diabetics have a high rate of SCD, with the rate for diabetic
women being slightly higher than that for diabetic men. Although there is
often greater obesity and higher blood pressure among diabetics, it is
likely that the disease also directly damages the small arteries of the
heart (14).

Studies have been made which correlate heart attacks and cardiac
arrests with psychological and social factors. External events can cause
fatal stress in many instances, but there are personality types which
can generate internal stress or high stress reactions to external events.
The most famous of these personality types is the
so-called "Type A behavior",
characterized by a high level of ambition, a chronic sense of time-urgency,
and a high susceptibility to anger. Most studies verify a correspondence of
"Type A behavior" with CAD, but there is not sufficient evidence for
believing that this personality type can be altered (17). One study
demonstrated that "Type A" subjects were significantly more likely to
live than other subjects ("Type B") if they survived the first 24 hours
following a primary coronary event (18).

CONTROLLABLE RISK FACTORS FOR SCD -- AN OVERVIEW

The most widely accepted and experimentally verified risk factors
for both coronary artery disease (CAD) and sudden cardiac death (SCD) are
the same: smoking, hypertension (high blood pressure) and
hypercholesterolemia (high blood cholesterol). Since CAD is the most
frequent trigger of SCD, this is not surprising. These three risk
factors are less pronounced and less well documented in women than they
are in men, so the discussion of controllable risk factors uses mainly
data from men.

According to the Framingham Study (13,14), the risk of SCD for men
is 3 times as great for a man who smokes over 20 cigarettes per day as
for a man who smokes none. The risk of SCD for a man with high blood
pressure (over 160/95) is nearly 3 times as great as for a man with
"normal" blood pressure (under 140/85). And the risk of SCD is
half as
great for a man with a blood cholesterol level of 197 mg/dl (milligrams per
tenth-of-a-litre, ie, per decilitre) as for a man with a level of 302 mg/dl
(with the relationship for all values in between being very nearly linear).
These data all apply to men in the 45-74 age group.

The effects of the three known controllable risk factors are
additive. A person with any two of the three CAD risk factors has 4½
times the mortality rate as someone with none. A person with all three
risk factors has 8½ times the mortality rate (19).

At least one study has denied that any CAD risk factors are
controllable (20). This view is contrary to that of the great majority
of researchers.

CONTROLLABLE RISK FACTORS FOR SCD -- SMOKING

Cigarette smoking is deemed to be responsible for 25% of all CAD
deaths in men under age 65, and 80% of all CAD deaths in men under age
45 (21). Nicotine has been implicated because it constricts blood vessels
and increases heart rate. However, it has been established by the
Framingham Study that filter cigarettes do not lower the rate of CAD
deaths (22). Thus, the effect of cigarettes on CAD is probably more due
to carbon monoxide, or to an unstudied tobacco compound, than to nicotine.
Carboxyhemoglobin (blood hemoglobin bound to carbon monoxide) lowers the
threshold for ventricular fibrillation in monkeys (22). Ten years after a
man stops smoking, his risk of CAD mortality is nearly the same as that
of a nonsmoker.

Part of the reason that the role of smoking in CAD and SCD has
been so poorly documented in Framingham and other long-term studies
is that very few women smoked when the study began, and those who did
smoke, frequently did not inhale.

The added risk of myocardial infarction (MI) and stroke among women
taking oral contraceptives is primarily among women over 35 and smokers.
The yearly incidence of MI among 100,000 women in their 30s was 6 & 2 for
users and non-users of contraceptives who smoke less than 14 cigarettes per
day. For those who smoke more than 15 cigarettes per day, the incidence was
30 & 11, respectively, for women in their 30s, and 246 & 61, respectively,
for women in their early 40s. The use of low-dose oral contraceptives has
reduced the incidence of stroke and MI by as much as 80% (23).

CONTROLLABLE RISK FACTORS FOR SCD -- HYPERTENSION

Ninety percent of cases of high blood pressure are described as
"essential hypertension". In this case, the word "essential" means "without
known cause", rather than "necessary". Of the three controllable risk factors
for SCD, only hypertension is also a proven risk factor for stroke (12,24).

Blood pressure is usually defined in terms of millimeters of mercury
(mm Hg), and is actually a measure of two blood pressures: systolic and
diastolic. Systolic pressure is the blood pressure when the heart is
exerting its maximum force of contraction on the blood, whereas diastolic
pressure is the pressure of the blood when the heart is relaxing between
beats. Blood pressure is usually expressed as systolic/diastolic, with
the upper limit of "normal" being around 140/85. Although elevated diastolic
pressure is normally regarded as more diagnostic of atherosclerosis, the
Framingham Study showed that elevated systolic and diastolic pressures are
equally risk factors for SCD (14). A study indicates that 27_% of men and
37_% of women aged 40 to 59 have blood pressures in excess of 160/95,
often regarded as the definitive boundary of "hypertension" (25).

Blood pressure rises with age for most North Americans, and this
is considered normal. Systolic pressures average 113, 123, 126, 132, 139
and 147 for American whites in their teens, 20s, 30s, 40s, 50s and 60s,
respectively. In one study (26), these figures are contrasted to the
systolic pressures of tribesmen in the Solomon Islands, which never
exceeds 120, even past the age of 60.

Overweight subjects in the upper third of the Metropolitan Life
relative weight charts had more than double the incidence of SCD than
subjects in the lower third (14). Nonetheless, obesity is not recognized
as a separate risk factor because it is so often associated with hypertension.
The Framingham Study showed that a 10% increase in weight results in a
6.5 mm Hg rise in systolic blood pressure (27). Another study found a
3 mm Hg and a 2 mm Hg increase in systolic and diastolic pressure
(respectively) for a 10 kg increase in body weight (25).

Despite the wide publicity given to the use of salt to reduce blood
pressure, there is considerable debate among researchers about the value of
salt reduction (28). Most agree that only a minority (15% to 25%) of the
population experiences a lowering of blood pressure with salt reduction, and
claims have been made that salt restriction can actually increase blood
pressure. The older (29) and obese (30) patients seem to be the most
sensitive to the effects of salt, possibly due to decreased kidney function.

Approaches to the control of blood pressure and atherosclerosis are
legion, and this is not the place to attempt an exhaustive study. Suffice
it to say that beta-blocking drugs and diuretics are frequently the first
choices by physicians for reducing blood pressure. The former reduces
adrenalin-like stimulation of the cardiovascular system, whereas the
latter simply reduces blood volume through increased urination. One study
estimated the reduction in CAD death through the use of beta-blockers for
a 10.5 year period to be 15% (31). Another study indicated that diuretics
increase the risk of arrhythmias (32).

It is worth noting that two studies have demonstrated reduction of
systolic blood pressure of 5 mm Hg by vegetarian diets lasting only a few
weeks (33,34).

CONTROLLABLE RISK FACTORS FOR SCD -- BLOOD CHOLESTEROL

The literature on blood cholesterol, both scientific and in the
popular press, is vast. It seems appropriate to begin the review here
with a summary of a well-researched feature article in TIME magazine (35).

Although a total blood cholesterol level in excess of 240 mg/dl is
regarded as high risk, the relative concentrations of HDL (high-density
lipoprotein) to LDL (low-density lipoprotein) cholesterol are crucial. Unlike
LDL cholesterol, which deposits cholesterol on artery walls, HDL actually
seems to remove cholesterol from artery walls. William Castelli, medical
director of the Framingham Heart Study, is quoted as saying, "If your
ratio is 4.5 or higher, you are running a ratio typical of people who develop
coronary heart disease in Framingham." For the average male heart patient,
the ratio is 5.4 to 6.1. The average marathon runner has a ratio of 3.4,
whereas the average vegetarian has a ratio of 2.5. A total blood cholesterol
level of under 200 mg/dl is not considered safe if the HDL is below 35 mg/dl.

A large 5-year study in Finland (which has one of the world's highest
heart-disease rates) showed that patients treated with the anticholesterol
drug gemfibrozil had an 11% decrease in LDL, an 11% increase in HDL and 34%
less heart disease. Niacin is reported to produce similar results. In another
study, eight sedentary men who were put on a regimen of rigorous exercise for
48 weeks showed a 5 mg/dl HDL increase and a 16% drop in blood triglycerides
(fats).

The Framingham Study found no influence of dietary cholesterol on
the concentration of cholesterol in the blood (36). Most blood cholesterol
is manufactured from the liver, and saturated fats seem to be the greatest
stimulus for liver production of LDL. Animal fats are notoriously high in
saturated fats, as are some "tropical oils" of plants (coconut and palm oil).
Monosaturated fats like olive and canola (rapeseed) oil have a neutral effect
on plasma lipid (fat) level (36).

Two polyunsaturated oils are regarded as "essential fatty acids"
(necessary in human diet): linoleic and linolenic acids. Linolenic acid
seems to be particularly effective in lowering VLDL (very low-density
lipoprotein -- a form of LDL laden with triglycerides). Linolenic acid is
a member of a family of polyunsaturates known as the omega-3 unsaturated
fatty acids, all of which are effective in lowering serum triglyceride. (The
"3" refers to the fact that the first double-bond occurs on the 3rd carbon
from the methyl end of the fatty acid. Linoleic acid is an omega-6
unsaturated fatty acid.) 55% of the fatty acid in linseed (also known as
flaxseed) oil
is linolenic acid. Most fish oils are high in omega-3 fatty acid, in
particular cod liver oil (25%) and mackerel oil (27%) (36).

Although many studies have verified that people with higher levels
of physical activity have a lower incidence of CAD (37), all such studies
have been criticized as providing only circumstantial evidence (38).
Nonetheless, a fairly impressive experiment was done on 27 monkeys under
observation for 36 months (39). The monkeys were divided into 3 groups of
9. One group served as a control, eating a normal diet of chow and living
a sedentary life. The other two groups were given chow "enriched" with
butter and cholesterol. One of those two groups was subjected to a one-hour
session of treadmill exercise 3 times weekly, and the other group remained
sedentary. All of the sedentary monkeys on the atherogenic diet (and none
of the others) showed electrocardiogram abnormalities -- and one such
monkey experienced an SCD after 23 months. The exercising monkeys showed
elevated HDL. LDL and VLDL levels in the exercising monkeys, although
still well above those seen in the controls, were significantly lower
than those seen in the sedentary, atherogenic-diet group. This latter
group showed marked atherosclerosis upon autopsy. The exercising monkeys
had lower resting heart-rates, larger hearts and had coronary arteries that
were "strikingly wider" than any of the sedentary monkeys. All monkeys
showed a similar systolic and diastolic pressure, irrespective of exercise
or diet.

In his book, RUNNING WITHOUT FEAR (40), Dr. Kenneth Cooper warns against
exercise that does not involve a proper warm-up and cool-down
period. Concerning the latter, it can be dangerous to suddenly stop
vigorous exercise, because the blood-stream still contains high levels
of adrenalin-like substances which can cause cardiac arrhythmias. Cooper
mentions the ancient Greek Pheidippides, who ran 26 miles from Marathon
to Athens to announce the defeat of the Persians, and promptly dropped dead
after he had done so. Cooper suggests that Pheidippides experienced an SCD
because he suddenly stopped running.

THE USE OF ASPIRIN AS PROTECTION AGAINST CAD

The Physicians Health Study (41) involved 22,071 physicians, half
of whom received a 325 mg dose of aspirin on alternate days, and half
of whom received an aspirin placebo. During the 5 years of the study there
were 164 cardiovascular deaths, with no statistically significant difference
between the two groups (81 in the aspirin group, 83 in the placebo group).
There were 10 deaths due to myocardial infarction (MI) in the aspirin
group, and 28 such deaths in the placebo group -- a statistically significant
difference. However, the differences for stroke (10 aspirin, 7 placebo) and
sudden cardiac death (22 aspirin, 12 placebo) were not regarded as
statistically significant. I am not a statistician, but the evidence would
lead me to believe that aspirin causes a statistically significant increase
in non-MI cardiovascular deaths, which nullifies the effect of the
significantly significant decrease in MI deaths.

EMERGENCY PROCEDURES

Although controversy still surrounds the use of CPR, the widely quoted
experiences in the Seattle area of Washington State (42,43) indicate that 43%
of cardiac arrest patients survive if CPR is initiated within 4 minutes and
definitive care is provided within 8 minutes. Survival is dramatically
reduced if either time is exceeded.

A very significant reduction in cardiac arrests among high risk
patients has been achieved by the use of small portable defibrillators. One
such device can be worn, and will automatically deliver a shock if heart
rate drops (44).

CONCLUSIONS

The use of exotic
life-extension methods
such as Deprenyl
seems almost
insignificant when contrasted to the real and high probability of fatality
due to cardiac arrest or heart attack. This is all the more sobering when
consideration is given to how greatly a cryonic suspension can be compromised
by a cardiac fatality. A serious life-extension program requires a careful
analysis of all the modes, dangers and probabilities of death.